RESUMEN
Early discoveries in chromatin biology and epigenetics heralded new insights into organismal development. From these studies, two mediators of cellular differentiation were discovered: the Polycomb group (PcG) of transcriptional repressors, and the trithorax group (trxG) of transcriptional activators. These protein families, while opposed in function, work together to coordinate the appropriate cellular developmental programs that allow for both embryonic stem cell self-renewal and differentiation. Recently, both the PcG and trxG chromatin modulators have been observed to be deregulated in a wide spectrum diseases including developmental disorders and cancer. To understand the impact of these findings we outline the past, present, and future. WIREs Dev Biol 2016, 5:659-688. doi: 10.1002/wdev.244 For further resources related to this article, please visit the WIREs website.
Asunto(s)
Biología Evolutiva , Enfermedad , N-Metiltransferasa de Histona-Lisina/metabolismo , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Proteínas del Grupo Polycomb/metabolismo , Animales , HumanosRESUMEN
RATIONALE: The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue from which they are released. Exosome transcriptomes may provide a better understanding of the rejection process. Furthermore, biomarkers originating from this transcriptome could provide timely and sensitive detection of acute cellular rejection (AR), reducing the incidence of severe AR and chronic lung allograft dysfunction and improving outcomes. OBJECTIVES: To provide an in-depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA population after lung transplantation and evaluate for differential expression between acute AR and quiescence. METHODS: Serial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed. MEASUREMENTS AND MAIN RESULTS: AR demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets. CONCLUSIONS: Our findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of AR and for biomarker discovery in lung transplantation.